Chlamydial organisms cause a wide spectrum of diseases in humans, other mammals and birds and have an enormous economic impact on both human and animal health and on agricultural industries worldwide. The two principal pathogens of humans are Chlamydia trachomatis and Chlamydophila pneumoniae. Chlamydia trachomatis is a cause of chronic conjunctivitis and is also the most common cause of sexually transmitted disease in humans. Chlamydophila pneumoniae causes acute respiratory disease and is responsible for 5 to 10% of the cases of community-acquired pneumonia, bronchitis and sinusitis. The organism has also been associated with chronic obstructive pulmonary disease, asthma, reactive airway disease, Reiter's syndrome, sarcoidosis and atherosclerosis.
Although antibiotics are available to Chlamydial infections, C. trachomatis infection remains asymptomatic in approximately 50% of infected men and approximately 70% of infected women. The major clinical manifestations of genital chlamydial infection in women include mucopurulent cervicitis, endometritis and pelvic inflammatory disease. Genital infection with C. trachomatis markedly enhances the risk for reproductive tract sequelae in women, including tubal factor infertility, chronic pain and ectopic pregnancy. Babies born to mothers with infection of their genital tract frequently present with chlamydial eye infection within a week of birth (chlamydial ophthalmia neonatorum), and may subsequently develop pneumonia.
In addition to the complications of genital chlamydia infection, C. trachomatis remains the leading cause of preventable blindness worldwide. Chronic ocular infections, referred to as trachoma, predominate in developing countries. It is estimated that 12 million people with trachoma will develop blindness by the year 2020, which has placed trachoma on the WHO priority list for intervention. Since 2001, the WHO has promoted control strategies including, for example, antibiotics, improved hygiene, and environmental measures, with limited success.
C. trachomatis infection is also a known co-factor for HIV/AIDS transmission. Epidemiological studies have linked genital chlamydial infection to an increased risk for acquisition of HIV disease. See, for instance, Brunham, R. C. et al., 1996, J. Infect. Dis. 173: 950-956 and Ghys, P. D. et al., 1997, AIDS 11: F85-F93. Immunosuppression due to HIV may lead to more aggressive chlamydial disease conditions like pelvic inflammatory disease in those who are infected with C. trachomatis. See, Thomas, K. et al., 2002, Hum. Reprod. 17:1431-1436.
Attempts in the 1950s and 1960s to develop a C. trachomatis vaccine capable of preventing infection and disease focused on immunization with crude formalin-killed whole chlamydia elementary body (EB) preparations or detergent extracts of EBs. Overall, the results of these trials demonstrated that a whole cell or detergent extract vaccine, while relatively safe, provided only a marginal benefit that was short-lived.
Following the identification of MOMP as the major protein component (approximately 60%) of the outer membrane in the early 1980s and the discovery that strong antibody responses are raised to that protein in infected animals and humans, vaccine studies focused on this protein. In the early 1990s, attention was turned to the development of recombinant MOMP vaccines. See, Longbottom, D., 2003, J. Med. Microbiol. 52:537-540. Although MOMP is highly immunogenic and can elicit a local neutralizing anti-Chlamydia antibody, most MOMP-specific neutralizing epitopes that have been mapped are located within the VD regions and thus give rise only to serovar-specific antibody. Attempts to combine serovar-specific epitopes in various vaccine vectors (e.g., poliovirus) to generate broadly cross-reactive neutralizing antibodies have been only marginally successful. See, for instance, Murdin, A. D. et al., 1993, Infect. Immun., 61:4406-4414 and Murdin, A.D. et al., 1995, Infect. Immun., 63:1116-1121).
Despite efforts to better understand the immune response in Chlamydial infections and efforts to develop an effective Chlamydial vaccine, a C. trachomatis vaccine has not been advanced into a Phase I clinical trial in over 40 years. Accordingly, a need exists for an effective vaccine to prevent and/or ameliorate Chlamydial infections and associated conditions such as trachoma.